Hair is a body protection organ which is recognized as an additional integument structure together with sebaceous glands, sweat glands and nails. Hair growth is a circulation process that is very well controlled. In mammals, the hair growth is defined as three distinct phases of anagen (growing phase), catagen (regressing phase), and telogen (resting phase). During the period of catagen, the regression of hair follicles reflects a strictly controlled process characterized by a matrix remodeling such as a terminal differentiation and apoptosis of proximal epithelial hair bulb, perifollicular proteolysis, and follicular melanogenesis completion.
Hair loss is a disease that emotionally gives a pain to humans. Also, the hair loss is associated with many diseases of human. There are many causes of hais loss, including diseases, nutritional deficiency, aging, hormonal imbalance, and stress.
Growth and development of the hair follicles interact with numerous growth factors and cytokines. The most well-known factors include, for example, keratinocyte growth factor (KGF) and interleukin-1 (IL-1). In particular, the control of interleukin-1 is related directly to the growth and development of the hair follicles.
Annually estimated market for hair growth amounts to billions of dollars. However, only two drugs for preventing hair loss, i.e., minoxidil which is anti-hypertensive potassium channel opener, and finasteride which is dihydrotestosteron-suppressing 5a-reductase inhibitor, have been approved by the FDA. Among them, minoxidil has no clear report on the mechanism of action, and side effects such as mild scalp irritation and allergic dermatitis have been reported. Also, only about 30% of patients showed the effect of hair growth, and there are no effects other than ordinary patients with alopecia areata. Further, finasteride is known to have a mechanism of action which inhibits an enzyme activity acting on androgen metabolism. Side effects such as sexual debility, erectile dysfunction, and women breasts have been reported. In particular, due to the toxicity inherent to the drug, its use for pregnant women is prohibited.
In Korea, a number of researches associated with hair loss are currently in progress. In recent years, the hair growth effects of cyclosporine A, an immunosuppressive agent, have been reported. However, due to a number of side effects, for example, a liver toxicity, a hypertension, an immunosuppressive effect, a renal toxicity, an increase in neutral lipid, it is hard to actually apply to a clinical therapy.
Therefore, the development of a medicine for treating hair loss which has a low toxicity or side effect and an excellent effect is urgent.
On the other hand, Cyclophilins (Cyps) were first found as proteins having a high affinity to the immunosuppressive cyclosporin A (CsA). The cyclophilins acts on various cellular responses including a transcriptional regulation, an immune response, a protein secretion and a mitochondrial function control.
Cyclophilins have a peptidyl-prolyl cis-trans isomerase (PPIase) activity which catalyzes the cis-trans conversion of peptide bond into a proline residue at amino-terminal which facilitates a protein folding and an additional cellular process. In mammals, more than ten cyclophilin subtypes are included. Cyclophilin A is a protein spreaded everywhere belonging to the immunophilin family. Numerous researches on the function of cyclophilin A have been made in some diseases such as cancer cell resistance, Alzheimer's disease and hepatitis C virus replication. Further, cyclosporin A is known to act as a growth factor in vascular smooth muscle cells.
However, in diseases related to hair loss, the role of CypA associated with the prevention of hair loss and the enhancement of hair growth has not been found.
Under this background, the present inventors have found that cyclophilin A having a PPIase activity, one of the immunophilin family, can be used to prevent hair loss or enhance hair growth.